Insulin conserves glucose while insulin resistance reduces the body?s conservation of glucose. Insulin resistance is associated with many health complications. Many people with insulin resistance develop diabetes. For unknown reasons, insulin resistance also promotes heart disease and breast cancer. Liver insulin resistance increases in the obese state partly because the expansion of fat tissue leads to low levels of circulating adiponectin. We are investigating the adiponectin pathway that increases insulin sensitivity in the liver. Our specific goals are to determine the role of (1) mTOR, a potential target of adiponectin and inhibitor of glucose production, (2) AMPK, a target of adiponectin that inhibits glucose production, (3) lysosome activity, a cellular process of protein degradation that provides amino acids for glucose production. The insight we gain could lead to a better understanding of adiponectin action in the liver and more effective interventions for the treatment of insulin resistance.[unreadable] [unreadable] [unreadable]